Work continues on structural studies of drug-nucleic acid crystalline complexes. Numerous comlexes have now been solved by X-ray crystallography. These include: 9-aminoacridine-iodoCpG, proflavine-iodoCpG, acridine orange-iodiCpG, ellipticine- iodoCpG, 3,5,6,8-tetramethyl-N-methy phenanthrolinium-iodoCpG, as well as ethidium-iodoCpG and ethidium-iodoUpA. These crystallographic studies have led to a series of models to understand the nature of drug-DNA (and RNA) binding. All models involve intercalation of the aromatic chromphore into the double helical polymer structures. Associated with intercalation is a conformational change in the sugar-phosphate backbone: C3' endo (3'-5') C2' endo. This conformational change has led to a detailed model to understand drug intercalation that requires an understanding of the dynamic nature of DNA (or RNA) structure. We have postulated the nature of the normal mode oscillation in these structures (due to thermal energies) that gives rise to the beta kinked DNA (or RNA) structure, a key intermediate in drug intercalation. This beta kinked structure corresponds to a second DNA structure (unlike the Watson-Crick structure), and normal mode oscillation in this structure gives rise to the intercalative geometry required for drug intercalation. The subject of drug intercalation is therefore intimately related to understand the subject of premelting (or DNA breathing), as we explain in our research proposal.